Third, although we were able to use pathway signatures from very different tissue contexts to predict pathway activation status, an examination of the initial proof-of-principle breast cancer examples revealed that the association of ER status to estrogen responsiveness as predicted using the osteosarcoma signature, although significant, was markedly weaker compared to the association of ER status to tamoxifen sensitivity predicted using a signature derived from the same tissue type (i.e. breast). The gene discussed is ESR1; the disease is osteosarcoma.